ACTG 388 - A Phase III Randomized, Controlled Trial of Efavirenz (EFZ) or Nelfinavir (NFV) in Combination with Fixed Dose Combination Lamivudine/Zidovudine (3TC/ZDV) and Indinavir (IDV) in HIV-Infected Subjects with < 200 CD4 Cells/mm3 or >100,000 HIV RNA Copies/ml in Plasma. This study will explore whether a four-drug regimen will be more successful than a three-drug regimen in suppressing HIV-1 replication in patients with advanced disease (CD4 <200 cells/mm3) or with very high virus loads (plasma HIV-1 RNA >100,000 copies/mL). A total of 444 subjects with HIV infection, < 200 CD4 cells/mm3 or >100,000 HIV RNA copies/ml of plasma and limited (no prior 3TC, NNRTIs or protease inhibitors) or no prior antiretroviral treatment will be enrolled. Subjects will be stratified by CD4 cell count (< 50 cells/mm3 versus > 50 cells/mm3) and plasma HIV RNA (,40,000 copies/ml versus > 40,000 copies/ml) in order to balance pretreatment CD4 cell counts and plasma HIV RNA levels and by prior antiretroviral therapy (no therapy versus any therapy). Subjects will be randomly assigned to one of three treatment arms: ARM I (N=148):3TC 150mg/ZDV 300 mg BID+IDV 800mg TID ARM II (N=148):3TC 150mg/ZDV 300mg BID+IDV 1000mg TID + EFZ 600mg QD ARM III (N=148):3TC 150mg/ZDV 300mg BID+IDV 1000mg BID+NFV 1250mg BID Subjects will be followed for 72 weeks beyond the enrollment of the last subject, unless the study is terminated early. Virologic response is defined as two consecutive HIV RNA level < 200 copies/ml. Virologic failure is defined as HIV RNA level > 200 copies/ml at Week 24 (if the preceding HIV RNA is > 200 copies/ml, a confirmatory value is not required at Week 24). Virologic relapse is defined as two consecutive HIV RNA level >200 copies/ml at any time following a virologic response. Subjects meeting the above criteria will have the option of continuing randomized study medications (Step 1 Treatment), switching to Step 2 Treatment (see below), switching to another ACTG study, or seeking best available therapy for the remaining weeks of the study (approximately 72 weeks from the enrollment of the last subject). Step 2 treatment will consist of: Abacavir (ABC) Amprenavir (APV) OR + Efavirenz (EFZ) + OR + PI 2 NRTIs another PI